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Expression of complement factor H binding immunoevasion proteins in Borrelia garinii isolated from patients with neuroborreliosis.
Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten). (Bergström)
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2005 (Engelska)Ingår i: Eur J Immunol, ISSN 0014-2980, Vol. 35, nr 10, s. 3043-3053Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The Lyme disease-pathogen Borrelia burgdorferi binds the complement inhibitor factor H (FH) to its outer surface protein E- (OspE) and BbA68-families of lipoproteins. In earlier studies, only serum-resistant strains of the genospecies B. burgdorferi sensu stricto or B. afzelii, but not serum-sensitive B. garinii strains, have been shown to bind FH. Since B. garinii often causes neuroborreliosis in man, we have readdressed the interactions of B. garinii with FH. B. garinii 50/97 strain did not express FH-binding proteins. By transforming the B. garinii 50/97 strain with an OspE-encoding gene from complement-resistant B. burgdorferi (ospE-297), its resistance to serum killing could be increased. OspE genes were detected and cloned from the B. garinii BITS, Pistoia and 40/97 strains by PCR and sequencing. The deduced amino acid sequences differed in an N-terminal lysine-rich FH-binding region from OspE sequences of resistant strains. Recombinant B. garinii BITS OspE protein was found to have a considerably lower FH-binding activity than the B. burgdorferi sensu stricto 297 OspE protein P21 (P21-297). Unlike bacteria that had been kept in culture for a long time, neurovirulent B. garinii strains from neuroborreliosis patients were found to express approximately 27-kDa FH-binding proteins. These were not recognized by polyclonal anti-OspE or anti-BbA68 antibodies. We conclude that B. garinii strains carry ospE genes but have a decreased expression of OspE proteins and a reduced ability to bind FH, especially when grown for prolonged periods in vitro. Recently isolated neuroinvasive B. garinii strains, however, can express FH-binding proteins, which may contribute to the virulence of neuroborreliosis-causing B. garinii strains.

Ort, förlag, år, upplaga, sidor
2005. Vol. 35, nr 10, s. 3043-3053
Nyckelord [en]
Amino Acid Sequence, Animals, Antigens; Bacterial/*genetics/immunology/metabolism, Bacterial Outer Membrane Proteins/*genetics/immunology/metabolism, Bacterial Proteins/*genetics/immunology/metabolism, Base Sequence, Borrelia burgdorferi Group/*pathogenicity/*physiology, Complement Factor H/immunology/metabolism, Humans, Immunoblotting, Lipoproteins/*genetics/immunology/metabolism, Lyme Neuroborreliosis/immunology/*metabolism, Molecular Sequence Data, Polymerase Chain Reaction, Surface Plasmon Resonance
Identifikatorer
URN: urn:nbn:se:umu:diva-12936PubMedID: 16208765OAI: oai:DiVA.org:umu-12936DiVA, id: diva2:152607
Tillgänglig från: 2007-10-03 Skapad: 2007-10-03 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Biology of Borrelia garinii Spirochetes
Öppna denna publikation i ny flik eller fönster >>Biology of Borrelia garinii Spirochetes
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Lyme borreliosis is a tick-transmitted infectious disease. The causative agents are spiral-shaped bacteria and the most common sign of infection is a skin rash at the site of the tick bite. If not treated with antibiotics, the bacteria can disseminate and cause a variety of different manifestations including arthritis, carditis or neurological problems. The disease is a zoonosis and the bacteria are maintained in nature by different vertebrate reservoir host animals. In Europe, three different Borrelia genospecies cause Lyme borreliosis: B. burgdorferi, B. afzelii and B. garinii. The latter depends in part on birds as its reservoir host. B. garinii bacteria have been found in a marine enzootic infection cycle worldwide and also among terrestrial birds. This thesis suggests that passerine birds and seabirds constitute an important reservoir for B. garinii bacteria also with clinical importance. We have found bacteria very similar to Lyme borreliosis causing isolates in ticks infesting migrating passerine birds. The birds not only transport infected ticks, but are competent reservoir hosts, as measured by their ability to infect naïve ticks. Their role as a reservoir host is dependent on their foraging behavior, where ground-dwelling birds are of greater importance than other species. When comparing B. garinii isolates from Europe, the Arctic and North Pacific, and including isolates from seabirds, passerine birds, Ixodes ricinus ticks and Lyme borreliosis patients, we found that phylogenetic grouping was not necessarily dependent on geographical or biological origin. B. garinii from seabirds were very heterogeneous and found in all different groups. Therefore, the marine and the terrestrial infection cycles are likely to overlap. This was supported by the fact that B. garinii isolated from seabirds can establish a long-term infection in mice. Bacteria from the genospecies B. garinii are overrepresented among neuroborreliosis patients. Interestingly, many clinical B. garinii isolates are sensitive to human serum and have shown weak binding to the complement inhibitor protein factor H. By transforming a serum-sensitive B. garinii isolate with a shuttle vector containing the gene for the factor H binding protein OspE from complement-resistant B. burgdorferi, serum resistance could be increased. In addition, neurovirulent B. garinii strains recently isolated from neuroborreliosis patients were shown to express a factor H binding protein, not found in bacteria that had been kept in culture for a long time. This protein may contribute to the virulence of neuroborreliosis-causing B. garinii strains. When testing B. garinii isolates from Lyme borreliosis patients and seabirds for resistance to human serum, all members of the latter group were sensitive to even low levels of serum. This suggests that seabird isolates are not capable of infecting humans. In agreement with this, B. garinii isolated from seabirds do not appear to bind human factor H.

Ort, förlag, år, upplaga, sidor
Umeå: Molekylärbiologi (Medicinska fakulteten), 2008. s. 73
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1161
Nyckelord
Borrelia garinii, Lyme borreliosis, birds, migration, reservoir host, complement, Ixodes ricinus, Europe, Asia, infection cycle
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-1578 (URN)978-91-7264-521-9 (ISBN)
Disputation
2008-03-28, Major Groove, 6L, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2008-03-14 Skapad: 2008-03-14 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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